Tirzepatide in Type 1 Diabetes: 23% Weight Loss Plus Heart and Kidney Benefits Over 21 Months

Off-label tirzepatide use in overweight adults with type 1 diabetes produced 23% weight loss, improved cardiovascular markers, and preserved kidney function over 21 months — benefits that persisted even after accounting for weight loss.

Garg, Satish K et al.·Diabetes technology & therapeutics·2025·Moderate EvidenceObservational
RPEP-11056ObservationalModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Observational
Evidence
Moderate Evidence
Sample
N=122
Participants
122 overweight/obese adults with type 1 diabetes (84 on tirzepatide, 38 matched controls) at a university hospital

What This Study Found

Over 21 months, 84 overweight/obese adults with type 1 diabetes using tirzepatide off-label lost an average of 59 pounds (23.4% body weight), while matched controls gained 1.7 pounds. HbA1c dropped 0.50% more in tirzepatide users versus controls. Beyond weight and blood sugar, tirzepatide significantly improved total cholesterol, LDL, triglycerides, systolic blood pressure, and preserved kidney function (eGFR).

Remarkably, the cardiovascular and kidney benefits remained statistically significant even after adjusting for weight loss and HbA1c changes — suggesting tirzepatide has direct protective effects on the heart and kidneys independent of its metabolic benefits. Controls saw significant eGFR decline over the same period.

Key Numbers

n=84 tirzepatide, n=38 controls · Weight loss: -59 lbs (-23.4%) vs +1.7 lbs · HbA1c: -0.50% vs -0.24% (p=0.017) · Improved: LDL, total cholesterol, triglycerides, systolic BP · eGFR preserved in tirzepatide, declined in controls · Duration: 21 months · Baseline BMI: 35.2 vs 33.3

How They Did This

Retrospective chart review of 84 overweight/obese adults with T1D prescribed tirzepatide since July 2022 (minimum 6 months use) at a university hospital. Controls (n=38) were frequency-matched for age, diabetes duration, sex, HbA1c, and BMI. Data from electronic medical records over 21 months. Linear mixed effects models examined changes in lipids, blood pressure, and eGFR over time, including models adjusted for weight and HbA1c changes.

Why This Research Matters

This is among the first long-term real-world data on tirzepatide use in type 1 diabetes, where it is not approved. Nearly two-thirds of adults with T1D are now overweight or obese, contributing to cardiovascular disease and kidney problems — yet they have few drug options beyond insulin. The finding that tirzepatide produced 23% weight loss, improved cardiovascular biomarkers, and preserved kidney function independently of metabolic improvements makes a compelling case for formal clinical trials.

The Bigger Picture

Tirzepatide (Mounjaro/Zepbound) is approved for type 2 diabetes and obesity but not type 1. This study adds to growing evidence that dual-incretin agonists may have a role in T1D, where obesity is increasingly common but treatment options are limited to insulin alone. The weight-independent cardiovascular and kidney benefits mirror findings in T2D studies and support the theory that GLP-1/GIP signaling has direct cardioprotective and nephroprotective effects. The authors call for a formal RCT.

What This Study Doesn't Tell Us

Retrospective observational design — not a randomized controlled trial, so confounding factors may explain some results. Tirzepatide users may have been more motivated or had different healthcare utilization patterns. Relatively small sample (84 + 38 controls) from a single center. Off-label prescribing means dosing may have varied. The study cannot prove causation for the weight-independent cardiovascular and kidney benefits.

Questions This Raises

  • ?Would a randomized controlled trial of tirzepatide in T1D confirm these cardiovascular and kidney benefits?
  • ?What is the optimal tirzepatide dose in type 1 diabetes, and how should insulin regimens be adjusted?
  • ?Are the weight-independent organ benefits driven by GLP-1 signaling, GIP signaling, or both?

Trust & Context

Key Stat:
-59 lbs (23.4%) weight loss Overweight adults with type 1 diabetes using tirzepatide for 21 months, with cardiovascular and kidney benefits independent of weight change
Evidence Grade:
This is a retrospective observational study with matched controls from a single center. While it provides valuable long-term real-world data, the lack of randomization and relatively small sample size limit the ability to draw causal conclusions. The authors appropriately call for a formal RCT.
Study Age:
Published in 2025 with data through early 2024, this is among the first long-term real-world reports of tirzepatide use in type 1 diabetes. It reflects current clinical practice where off-label prescribing is occurring ahead of formal trials.
Original Title:
Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.
Published In:
Diabetes technology & therapeutics, 27(3), 152-160 (2025)
Database ID:
RPEP-11056

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Watches what happens naturally without intervening.

What do these levels mean? →

Frequently Asked Questions

Is tirzepatide approved for type 1 diabetes?

No. Tirzepatide (sold as Mounjaro for diabetes and Zepbound for weight loss) is only approved for type 2 diabetes and obesity. This study examined off-label use in type 1 diabetes patients, which some endocrinologists are prescribing to help with weight and metabolic control. The authors strongly recommend formal clinical trials.

How can heart and kidney benefits be independent of weight loss?

GLP-1 and GIP receptors are found directly in heart tissue, blood vessels, and kidneys. Tirzepatide activates both receptors, which appears to reduce inflammation, improve blood vessel function, and protect kidney cells through mechanisms separate from weight loss. This explains why cardiovascular and kidney improvements persisted even after statistically removing the effect of weight change.

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Cite This Study

RPEP-11056·https://rethinkpeptides.com/research/RPEP-11056

APA

Garg, Satish K; Kaur, Gurleen; Renner, Drew; Lanning, Monica S; Mason, Emma; Beatson, Christie; Ciesco, Kelly; Snell-Bergeon, Janet. (2025). Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.. Diabetes technology & therapeutics, 27(3), 152-160. https://doi.org/10.1089/dia.2024.0481

MLA

Garg, Satish K, et al. "Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.." Diabetes technology & therapeutics, 2025. https://doi.org/10.1089/dia.2024.0481

RethinkPeptides

RethinkPeptides Research Database. "Cardiovascular and Renal Biomarkers in Overweight and Obese ..." RPEP-11056. Retrieved from https://rethinkpeptides.com/research/garg-2025-cardiovascular-and-renal-biomarkers

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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.